The human .beta..sub.3 -adrenergic receptor (.beta..sub.3 receptor) gene was discovered in 1989 (L. J. Emorine et al., Sci. 245, 1989, 1118-1120). The .beta..sub.3 receptor protein is widely considered to be a target for agents that will be useful as human therapeutics (J. R. S. Arch et al., Nature 309, 1984, 163-165), as well as for agents that beneficially alter the meat and fat content of feed animals. It has been believed and repeatedly published by those that originally described the .beta..sub.3 receptor gene that the rodent and human .beta..sub.3 receptor genes were intronless and that the human gene contained a single exon that encoded a protein of 402 amino acids (Emorine et al., ibid; L. J. Emorine et al, Biochem. Pharmacology 41, 1991, 853-859; L. J. Emorine et al., Am. J. Clin. Nutr. 55 1992, 215S-218S; and C. Nahmias et al. EMBO Journal 10, 1991, 3721-3727). DNA constructs have been made that are based upon the assumption that the human .beta..sub.3 receptor gene contains only 402 amino acids, and these constructs have demonstrated commercial value as reagents for the development of compounds that specifically interact with the .beta..sub.3 receptor protein.
We have discovered that the assumption that the human .beta..sub.3 receptor gene contains only one protein-coding block is incorrect. Specifically, we have discovered that the human, rat and mouse .beta..sub.3 receptor genes contain two protein-coding exons. Thus, the amino acid sequence of the human and mouse .beta..sub.3 -adrenergic receptor proteins that were previously deduced from genomic DNA are incomplete. Most significantly, we have discovered that the human .beta..sub.3 receptor gene is 6 amino acids larger than previously believed. Because we have cloned the human receptor cDNA, we have, for the first time, elucidated the correct amino acid sequence of the human .beta..sub.3 receptor. (SEQ. ID. NO. 1)